The Future of Neuroscience Education

I spent the majority of my career in medical education and saw significant changes over time.

One encouraging sign was the emergence of neuroscience as a respected and beneficial academic discipline.

Now, a new perspective on Neuroscience Training for the 21st Center has been written by Huda Akil and colleagues. This perspective is recently published in the journal Neuron with free access to the full-text manuscript.

Here are my notes from reading this perspective. Readers can access the free full-text manuscript by clicking on the link in the citation below.

Two important challenges for the field

• Incorporating data and statistical skills traininng in neuroscience
• Integration of other scientific disciplines in neuroscience research (engineering, CS)

Need to improve trainee skills in high-level programming languages (i.e. MATLAB)

Enhanced communication skills in training are needed to address publication and grant-writing challenges

Improvement is needed in "enabling the process by which basic science discoveries add fundamental knowledge to the field and inform solutions for disabiling neurological and psychiatric conditions". 

The above goal can be met by integrating collaborative training of basic and clinical neuroscience trainees.

Neuroscience trainees will need to be trained to meet demands of job availability
Number of neuroscience Ph.Ds graduate greatly exceed number of academic faculty slots
Federal research funding is unable to meet needs of many neuroscience graduates
However, non-academic private positions in neuroscience are expanding providing optimism for many neuroscience Ph.Ds

Key roles exist in multiple sectors to attract and train the best and brightest

• Academia
• Private sector
• Societies and Patient-Advocacy Organizations
• NIH, NSF and other funding agencies

These agencies must plan and work together to "ensure the success of this next generation of neuroscientists"

My Commentary

This is an outstanding summary of the challenges and opportunities for neuroscience education. As a physician I am particularly excited about clinical opportunities for integrating basic neuroscience training the the medical setting. I have recently been thinking about how a name change for neurology and psychiatry might aid in this evolution. Stay tuned for a provocative post on a new integrated neuroscience medicine discipline.

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Akil, H., Balice-Gordon, R., Cardozo, D., Koroshetz, W., Posey Norris, S., Sherer, T., Sherman, S., & Thiels, E. (2016). Neuroscience Training for the 21st Century Neuron, 90 (5), 917-926 DOI: 10.1016/j.neuron.2016.05.030

Pain Prevalence in Dementia

The development of speech and language impairment in dementia presents barriers in many clinical domains.

One important clinical domain is assessment and management of pain. Dementia may preclude spontaneous or interview-elicited pain reporting.

A report today in MedicalXpress noted reduced reporting of pain in patients with diabetes and cognitive impairment.

I was able to locate one free full-text manuscript reviewing the prevalence of pain in various types of dementias. This literature review found the following:

• Pain prevalence was estimated at 46% of Alzheimer's disease patients
• Pain prevalence was estimated at 56% of vascular dementia patients
• Pain prevalence was estimated at 53% in mixed dementia patients
• Insufficient research study was found for determining rates of pain in frontotemporal and Lewy body dementia populations

These studies support rigorous pain assessment and monitoring for pain in dementia patient populations. Alert clinicians and nurses can aid in proxy assessment of pain when speech and language impairments reduce pain self reporting.

You can access this full text review manuscript by clicking on the PMID in the citation below.

I found a helpful education sheet produced by the Australian government on pain in dementia. This sheet included a list of potential non-verbal signs of pain in later stages of dementia including:

• Facial grimacing
• Moaning or crying out with movement
• Increased heart rate, blood pressure or sweating
• Changes in sleep patterns including increased or restless sleep
• Changes in behavior including increased irritability or aggression.

You can access the Pain and Dementia Education in the Dementia Q&A section at this link. 

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van Kooten J, Binnekade TT, van der Wouden JC, Stek ML, Scherder EJ, Husebø BS, Smalbrugge M, & Hertogh CM (2016). A Review of Pain Prevalence in Alzheimer's, Vascular, Frontotemporal and Lewy Body Dementias. Dementia and geriatric cognitive disorders, 41 (3-4), 220-32 PMID: 27160163

The Promise of DTI (Imaging) in Neurology

Brain diffusion tensor imaging (DTI) is emerging as new important brain imaging tool in research.

Clinicial applications of DTI are lagging the research applications in development.

However, clinical applications are coming.

The Radiological Society of North America recently published a summary of potential application for DTI in Neurology on their website. You can access the website post HERE.

Three key areas were highlighted in this post including use of DTI for:

• Aiding Identification of Prognosis in Mild TBI
• Gender Effects on Sports-Related Head Injury
• Brain Mapping Neurosurgery

Included at the website are two You Tube Videos. Here is the video related to using DTI as a prognostic aid in TBI.

Dr. ML Lipton featured in the You Tube video has a free full-text published a study of DTI in soccer heading in the manuscript cited below. Click on the PMID to get to the manuscript.

In this manuscript the authors were able to identify change in white matter brain microstructure related to prevalence of soccer heading independent of concussion.

Image of white matter corona radiata is my screen shot from the iPad app Brain Tutor.

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Lipton ML, Kim N, Zimmerman ME, Kim M, Stewart WF, Branch CA, & Lipton RB (2013). Soccer heading is associated with white matter microstructural and cognitive abnormalities. Radiology, 268 (3), 850-7 PMID: 23757503

Prenatal Smoking and Offspring Schizophrenia

The topic prevention of brain disorders  is commonly neglected. This is despite increasing evidence for evidence-based support for prevention opportunities.

This issue is highlighted in a recent study out of Finland that examined prenatal nicotine metabolite levels and offspring diagnosis of schizophrenia.

In this study, Solja Niemela and the Finnish research team examined all live births in Finland between 1983 and 1998.

What makes this study powerful is the measurement of maternal serum cotinine levels in maternal serum during the early and mid stages of prenancy. Cotinine is a metabolite and the levels of cotinine reflect the level of nicotine consumption.

The key findings from this study include the following points:

• Measuring cotinine levels as a continuous variable yielded an increased odds ratio for schizophrenia of 3.41 (95% CI 1.86-6.24)
• Mothers in the highest cotinine level group had a 38% increase in offspring schizophrenia rates
• These findings included controlling for potential confounding variables including maternal age and parental history of psychiatric disorders

Interestingly a PubMed search found a second study linking maternal smoking with increased risk of offspring diagnosis of bipolar disorder (odds ratio 2.01, 95% CI 1.48-2.53).

These two studies in combination support a potential non-specific effect of prenatal nicotine exposure on risk for two of the most impairing psychiatric disorders. 

These two studies also support aggressive smoking cessation efforts in young women before pregnancy or at the latest very early after conception.

You can find more information about these two studies by clicking on the citation links below.

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Niemelä, S., Sourander, A., Surcel, H., Hinkka-Yli-Salomäki, S., McKeague, I., Cheslack-Postava, K., & Brown, A. (2016). Prenatal Nicotine Exposure and Risk of Schizophrenia Among Offspring in a National Birth Cohort American Journal of Psychiatry DOI: 10.1176/appi.ajp.2016.15060800

Talati A, Bao Y, Kaufman J, Shen L, Schaefer CA, & Brown AS (2013). Maternal smoking during pregnancy and bipolar disorder in offspring. The American journal of psychiatry, 170 (10), 1178-85 PMID: 24084820

Free Alcohol Use Reduction App

An investigational app and online program to reduce alcohol intake is now available free to the public.

This tool is an application of cognitive bias modification. A link to a study supporting cognitive bias modification is noted in the citation below. Click on the PMID link to get to the abstract.

The program uses a 15 minutes per day tool for four days.

The program was developed at the London School of Economics by Professor Paul Dolan.

Users who sign up to use the tool will be providing data to further determine the effectiveness of the app.

Read more about this tool at Science Daily HERE.

A link to the program and app can be found HERE.

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Photo of painting titled "Peasants Enjoying a Beer at Pub in Fribourg" is from Wikipedia Creative Common file. Citation: By François Louis Jaques (1877–1937) (Beurret & Bailly) [Public domain], via Wikimedia Commons

Gladwin TE, Rinck M, Eberl C, Becker ES, Lindenmeyer J, & Wiers RW (2015). Mediation of cognitive bias modification for alcohol addiction via stimulus-specific alcohol avoidance association. Alcoholism, clinical and experimental research, 39 (1), 101-7 PMID: 25623410

A New Chromosome Y Risk for Alzheimers

There are many risk factors for Alzheimer's Disease (AD) including history of head trauma and family history of AD.

The strongest risk factor is advanced age. Yearly risk for AD is about 1% per year in 70 year old populations jumping to around 7% in 90 year old groups.

Now a recent study is shedding some light on a new risk for AD in men. This risk appears to be related to a chromosome Y phenomenon known to be associated with aging.

Elderly men show a tendency to lose the Y chromosome from a small percentage of cells over time. This phenomenon is known as loss of Y or LOY.

The percentage of blood cells with LOY can be determined. A study recently published in Journal of Human Genetics (see citation below) found significant support for higher percentage of LOY being linked to AD risk.

Here are the key findings:

• In a sample of 3218 elderly men 17% showed evidence of LOY chromosome mosaicism
• LOY percentage rates were strongly positively correlated with older age
• Men with AD had higher rates of LOY than age-matched men without AD (adjusted odds ratio=2.80)
• Two prospective studies found higher rates of incident AD in men with LOY (adjusted odds ratio=6.80)

These findings are not simply minor as the effect of LOY on risk appears similar in magnitude to the strongest genetic risk factor for AD, APOE gene status.

LOY has also been linked to a higher risk of cancer, so it appears to be a non-specific risk factor.

The authors of this study note;

"Regardless of the underlying mechanism(s) for the increased risk of AD and cancer in men with LOY in blood, our and other's published results reinforce a role of factors on chromosome Y in various, still poorly explored biological processes, other than sex determination and sperm production."

LOY is not yet a common test in clinical practice. However, I think we will be hearing much more on this association with potential for screening and intervention studies.

Access the free full-text manuscript by clicking on the DOI link in the citation below.

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d sperm production.

Dumanski JP et al (2016). Mosiac loss of chromosome Y in blood is associated with Alzheimer's disease American Journal of Human Genetics : 10.1016/j.ajhg.2016.05.014

Does Flu Vaccination Reduce Dementia Risk?

In my daily review of neuroscience news I ran across an article flu vaccination and dementia risk in heart failure.

This study was reported at the 3rd World Congress on Acute Heart Failure by Dr. Ju-Chi Liu from Taipei Medical University.

So how might influenza vaccination be related to dementia risk?  We do know acute influenza infection reaches the brain causing headache and increasing brain inflammation, at least temporarily. We also know brain inflammation may be involved in the mechanism of amyloid and tau protein deposition in the brain. So this link has some potential biological plausibility.

In the Taiwanese study, 20,509 subjects with a diagnosis of heart failure were followed via centralized records. About half received flu vaccination during follow up. Subjects receiving at least one flu vaccination had a 35% lower rate of dementia diagnosis compared to those not receiving any vaccination. Subjects receiving three or more vaccinations had a 55% lower risk of recorded dementia diagnosis on follow up.

I went to PubMed looking for more research for this association and a similar finding has been published by the same research group in a free full-text manuscript in patients with chronic kidney disease (CKD). The key elements of this study were:

• Subjects: All 32,844 individuals with a chronic kidney disease diagnosis in the Taiwan National Health Insurance Research Database. From this set 11,843 subjects had sufficient data for the study.
• Case definition: Influenza vaccination during the study period
• Outcome definition: Research database definition of dementia during follow up period
• Results: After controlling for confounding variables, influenza vaccination case subjects had a 36% lower rate of dementia diagnosis compared to those not vaccinated (odds ratio=.64)

Interestingly, there appeared to be a dose dependent effect with those receiving multiple influenza vaccinations showing even lower rates of dementia.

Also, somewhat unexpectedly, vaccinations given outside of the typical influenza season showed a greater effect.

The authors note in their discussion:

"In clinical practice, we suggest that CKD patients with high dementia risk be vaccinated."

The authors note dementia risk is increased in CKD with hypertension, high blood cholesterol and diabetes.

The most important potential implication in these two studies, is whether influenza might reduce dementia risk in the general non-medically ill population. I think we will have more research on this issue soon.

There are many reasons for regular influenza vaccination. Preserving brain health may be another important reason for expanded vaccination efforts.

You can access the free full-text manuscript of the CKD and dementia paper by clicking on the PMID link in the citation below.

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Figure of influenza virus in post is from Wikipedia Creative Commons file authored by: National Institutes of Health; originally uploaded to en.wikipedia by TimVickers (25 October 2006), transferred to Commons by Quadell using CommonsHelper

Liu JC, Hsu YP, Kao PF, Hao WR, Liu SH, Lin CF, Sung LC, & Wu SY (2016). Influenza Vaccination Reduces Dementia Risk in Chronic Kidney Disease Patients: A Population-Based Cohort Study. Medicine, 95 (9) PMID: 26945371